Gland size is associated with changes in gene expression profiles in sporadic parathyroid adenomas

Jennifer E. Rosen, Nick G. Costouros, Dominique Lorang, A. Lee Burns, H. Richard Alexander, Monica C. Skarulis, Craig Cochran, James F. Pingpank, Stephen J. Marx, Allen M. Spiegel, Steven K. Libutti

Research output: Contribution to journalArticle

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Abstract

Background: Sporadic parathyroid adenomas (SPAs) are benign neoplasms responsible for most cases of primary hyperparathyroidism (pHPT). The molecular pathways responsible for the variations in clinical severity of pHPT are unknown. We studied gene expression profiles in patients with SPAs and pHPT to determine associations between these changes and clinical parameters. Methods: We selected 10 patients with solitary SPAs and nonfamilial, non-MEN1 pHPT treated with surgery from 2001 to 2003. Pathologic and clinical data were reviewed. At operation, tissues from SPAs were frozen in liquid nitrogen; total RNA was obtained from sections, and the diagnosis was confirmed with hematoxylin and eosin staining. Control normal parathyroid RNA was age- and sex-matched. RNA was amplified, labeled, and hybridized to a microarray of 22,272 human oligonucleotides. Cluster analysis of gene expression, analysis of expression ratios, and comparison of clinical parameters were performed. Results: All patients were cured; all specimens were consistent with SPAs. K means clustering divided the 10 patients into 2 distinct 5-patient gene expression groups by using uncentered correlation based on gene subgrouping. Of the clinical parameters, only the mean gland volume was significantly different between group 1 (390∈±∈160 mm3) and group 2 (1080∈± ∈615 mm3; P = .032 by Mann-Whitney test). Seventy-five genes were significantly upregulated or downregulated (with a ratio of <.33 or >3) compared with controls. These genes included the v-fos viral oncogene homolog and six calcium ion-binding signaling proteins. Conclusions: Differential expression of a few critical genes may contribute to differences in gland volume in SPAs. A better understanding of these pathways may help to define the pathophysiology of pHPT.

Original languageEnglish (US)
Pages (from-to)1-5
Number of pages5
JournalAnnals of Surgical Oncology
Volume12
Issue number5
DOIs
StatePublished - May 2005
Externally publishedYes

Fingerprint

Parathyroid Neoplasms
Transcriptome
Primary Hyperparathyroidism
RNA
Genes
Cluster Analysis
fos Genes
Gene Expression
Hematoxylin
Eosine Yellowish-(YS)
Oligonucleotides
Carrier Proteins
Nitrogen
Down-Regulation
Ions
Staining and Labeling
Calcium
Neoplasms

Keywords

  • Gene expression profile
  • Microarray analysis
  • Parathyroid adenoma
  • Primary hyperparathyroidism

ASJC Scopus subject areas

  • Surgery
  • Oncology

Cite this

Rosen, J. E., Costouros, N. G., Lorang, D., Lee Burns, A., Alexander, H. R., Skarulis, M. C., ... Libutti, S. K. (2005). Gland size is associated with changes in gene expression profiles in sporadic parathyroid adenomas. Annals of Surgical Oncology, 12(5), 1-5. https://doi.org/10.1245/ASO.2005.03.103

Gland size is associated with changes in gene expression profiles in sporadic parathyroid adenomas. / Rosen, Jennifer E.; Costouros, Nick G.; Lorang, Dominique; Lee Burns, A.; Alexander, H. Richard; Skarulis, Monica C.; Cochran, Craig; Pingpank, James F.; Marx, Stephen J.; Spiegel, Allen M.; Libutti, Steven K.

In: Annals of Surgical Oncology, Vol. 12, No. 5, 05.2005, p. 1-5.

Research output: Contribution to journalArticle

Rosen, JE, Costouros, NG, Lorang, D, Lee Burns, A, Alexander, HR, Skarulis, MC, Cochran, C, Pingpank, JF, Marx, SJ, Spiegel, AM & Libutti, SK 2005, 'Gland size is associated with changes in gene expression profiles in sporadic parathyroid adenomas', Annals of Surgical Oncology, vol. 12, no. 5, pp. 1-5. https://doi.org/10.1245/ASO.2005.03.103
Rosen, Jennifer E. ; Costouros, Nick G. ; Lorang, Dominique ; Lee Burns, A. ; Alexander, H. Richard ; Skarulis, Monica C. ; Cochran, Craig ; Pingpank, James F. ; Marx, Stephen J. ; Spiegel, Allen M. ; Libutti, Steven K. / Gland size is associated with changes in gene expression profiles in sporadic parathyroid adenomas. In: Annals of Surgical Oncology. 2005 ; Vol. 12, No. 5. pp. 1-5.
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abstract = "Background: Sporadic parathyroid adenomas (SPAs) are benign neoplasms responsible for most cases of primary hyperparathyroidism (pHPT). The molecular pathways responsible for the variations in clinical severity of pHPT are unknown. We studied gene expression profiles in patients with SPAs and pHPT to determine associations between these changes and clinical parameters. Methods: We selected 10 patients with solitary SPAs and nonfamilial, non-MEN1 pHPT treated with surgery from 2001 to 2003. Pathologic and clinical data were reviewed. At operation, tissues from SPAs were frozen in liquid nitrogen; total RNA was obtained from sections, and the diagnosis was confirmed with hematoxylin and eosin staining. Control normal parathyroid RNA was age- and sex-matched. RNA was amplified, labeled, and hybridized to a microarray of 22,272 human oligonucleotides. Cluster analysis of gene expression, analysis of expression ratios, and comparison of clinical parameters were performed. Results: All patients were cured; all specimens were consistent with SPAs. K means clustering divided the 10 patients into 2 distinct 5-patient gene expression groups by using uncentered correlation based on gene subgrouping. Of the clinical parameters, only the mean gland volume was significantly different between group 1 (390∈±∈160 mm3) and group 2 (1080∈± ∈615 mm3; P = .032 by Mann-Whitney test). Seventy-five genes were significantly upregulated or downregulated (with a ratio of <.33 or >3) compared with controls. These genes included the v-fos viral oncogene homolog and six calcium ion-binding signaling proteins. Conclusions: Differential expression of a few critical genes may contribute to differences in gland volume in SPAs. A better understanding of these pathways may help to define the pathophysiology of pHPT.",
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AU - Costouros, Nick G.

AU - Lorang, Dominique

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AU - Alexander, H. Richard

AU - Skarulis, Monica C.

AU - Cochran, Craig

AU - Pingpank, James F.

AU - Marx, Stephen J.

AU - Spiegel, Allen M.

AU - Libutti, Steven K.

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N2 - Background: Sporadic parathyroid adenomas (SPAs) are benign neoplasms responsible for most cases of primary hyperparathyroidism (pHPT). The molecular pathways responsible for the variations in clinical severity of pHPT are unknown. We studied gene expression profiles in patients with SPAs and pHPT to determine associations between these changes and clinical parameters. Methods: We selected 10 patients with solitary SPAs and nonfamilial, non-MEN1 pHPT treated with surgery from 2001 to 2003. Pathologic and clinical data were reviewed. At operation, tissues from SPAs were frozen in liquid nitrogen; total RNA was obtained from sections, and the diagnosis was confirmed with hematoxylin and eosin staining. Control normal parathyroid RNA was age- and sex-matched. RNA was amplified, labeled, and hybridized to a microarray of 22,272 human oligonucleotides. Cluster analysis of gene expression, analysis of expression ratios, and comparison of clinical parameters were performed. Results: All patients were cured; all specimens were consistent with SPAs. K means clustering divided the 10 patients into 2 distinct 5-patient gene expression groups by using uncentered correlation based on gene subgrouping. Of the clinical parameters, only the mean gland volume was significantly different between group 1 (390∈±∈160 mm3) and group 2 (1080∈± ∈615 mm3; P = .032 by Mann-Whitney test). Seventy-five genes were significantly upregulated or downregulated (with a ratio of <.33 or >3) compared with controls. These genes included the v-fos viral oncogene homolog and six calcium ion-binding signaling proteins. Conclusions: Differential expression of a few critical genes may contribute to differences in gland volume in SPAs. A better understanding of these pathways may help to define the pathophysiology of pHPT.

AB - Background: Sporadic parathyroid adenomas (SPAs) are benign neoplasms responsible for most cases of primary hyperparathyroidism (pHPT). The molecular pathways responsible for the variations in clinical severity of pHPT are unknown. We studied gene expression profiles in patients with SPAs and pHPT to determine associations between these changes and clinical parameters. Methods: We selected 10 patients with solitary SPAs and nonfamilial, non-MEN1 pHPT treated with surgery from 2001 to 2003. Pathologic and clinical data were reviewed. At operation, tissues from SPAs were frozen in liquid nitrogen; total RNA was obtained from sections, and the diagnosis was confirmed with hematoxylin and eosin staining. Control normal parathyroid RNA was age- and sex-matched. RNA was amplified, labeled, and hybridized to a microarray of 22,272 human oligonucleotides. Cluster analysis of gene expression, analysis of expression ratios, and comparison of clinical parameters were performed. Results: All patients were cured; all specimens were consistent with SPAs. K means clustering divided the 10 patients into 2 distinct 5-patient gene expression groups by using uncentered correlation based on gene subgrouping. Of the clinical parameters, only the mean gland volume was significantly different between group 1 (390∈±∈160 mm3) and group 2 (1080∈± ∈615 mm3; P = .032 by Mann-Whitney test). Seventy-five genes were significantly upregulated or downregulated (with a ratio of <.33 or >3) compared with controls. These genes included the v-fos viral oncogene homolog and six calcium ion-binding signaling proteins. Conclusions: Differential expression of a few critical genes may contribute to differences in gland volume in SPAs. A better understanding of these pathways may help to define the pathophysiology of pHPT.

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